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E J Roy

Publications and source records attributed to E J Roy.

At least 37 records · Page 2Linked to original sources

Retention of masculine sexual behavior following castration in male B6D2F1 mice.

The reduction of masculine sexual behavior following castration varies widely among genotypes. In contrast to the loss of sexual behavior by castrated males of other strains, males of the B6D2F1 genotype retain the ejaculatory reflex for many weeks after castration. The present study examined this retention phenomenon. Masculine sexual behaviors were measured before and after castration or sham operation in male C57BL/6J, DBA/2J, and B6D2F1 mice. Castrated C57BL/6J and DBA/2J males showed a rapid decline in copulatory behavior. In contrast, 30% of the B6D2F1 males continued to ejaculate 25 weeks after castration. Regardless of whether or not sexual behaviors were retained, levels of plasma testosterone and hypothalamic nuclear estrogen receptors were reduced by castration. These results suggest that the intra- and inter-strain differences in the retention of sexual behavior following castration are not due to differences in levels of steroid hormones. Further, some B6D2F1 males retain the ability to copulate in the absence of gonadal hormone levels required for the maintenance of sexual behavior in other genotypes.

Animals↗

Endogenous aldosterone and corticosterone in brain cell nuclei of adrenal-intact rats: regional distribution and effects of physiological variations in serum steroids.

In vivo brain uptake of labeled aldosterone (ALD) and corticosterone (CORT) in adrenalectomized (ADX) rats indicates a strong cell-nuclear localization of both hormones, predominantly in the hippocampus. The primarily limbic concentration of these hormones is also supported by in vitro assays of ALD and CORT binding in cytosol from ADX rats. However, assays of binding in tissues from ADX rats often fail to account for the normal competition of assorted corticosteroids for binding sites in the adrenal-intact subject. Because the binding affinity of corticoid receptors for CORT is greater than, or equivalent to that for ALD, and plasma concentrations of CORT exceed ALD levels, it is possible that ALD is not actually concentrated by brain cell-nuclei in the normal, adrenal-intact subject. Moreover, description of the brain's in vivo regional uptake of ALD or CORT in ADX rats may reflect labeling of heterogeneous binding sites by the single corticosteroid ligand ([3H]ALD or [3H]CORT) under investigation. Research using subcellular fractionation and radioimmunoassay (RIA) has demonstrated the presence of endogenously secreted CORT in brain cell nuclei of adrenal-intact rats, and confirmed the principally limbic localization of endogenous CORT in the brain. In the present study, subcellular fractionation and RIA were employed to determine whether endogenously secreted ALD is concentrated by cell nuclei of the brain in adrenal-intact rats, and to assess the regional variation in the brain's cell-nuclear uptake of endogenously secreted ALD. Cell-nuclear CORT levels were also measured in this experiment to assess the possible competition between ALD and CORT for brain cell-nuclear uptake. Circadian rhythms, stress and dietary sodium were utilized in this study to induce physiological variations in serum ALD and CORT. Endogenous ALD was found in the nuclear fraction of all brain tissues tested, indicating that ALD is bound and translocated to brain cell nuclei in the presence of normal corticosteroid competition. However, brain cell-nuclear ALD appeared not to vary as a function of physiological variation in serum ALD, suggesting that the receptor population was saturated under most normal circumstances. Unexpectedly, the highest cell-nuclear concentrations of endogenous ALD were found in the hypothalamus, rather than hippocampus. This finding suggests that the predominantly hippocampal localization of ALD observed in previous in vivo autoradiographic studies may have provided an inaccurate profile of the loci of ALD action in brain by failing to control for competitive binding by other corticosteroids in the adrenal-intact preparation.

Adrenalectomy↗

Effective intervals for the administration of estradiol pulses and the induction of sexual behavior in female rats.

The interval between two pulses of estradiol was varied and subsequent progesterone-facilitated female sexual behavior was observed. The total dose of estradiol (2 micrograms free estradiol) has been shown previously to elicit little receptivity when administered in a single pulse. In the present study, two pulses of 1.0 microgram free estradiol separated by anywhere from 3-36 hours induced high levels of progesterone-facilitated receptivity when observed 18 hours after the second estrogen pulse. Various intervals between the second estrogen pulse and the time of testing were also evaluated. Female rats tested at 18, 24 and 36 hours after the second estrogen pulse (plus progesterone) were highly receptive. These results raise new possibilities about the time course of cellular events underlying the estrogen induction of feminine sexual behavior.

Animals↗

Asymmetry in responsiveness of the hypothalamus of the female rat to estradiol.

Asymmetry of function is an increasingly general principle of neuroanatomy, and right-left asymmetry has been observed in some neuroendocrine functions. We report that the right side of the hypothalamus of female rats is more responsive to estradiol than the left side of the hypothalamus for the induction of sexual receptivity. These results are consistent with previous suggestions that the left side of the hypothalamus is more sensitive to the defemininizing actions of neonatal hormones.

Animals↗

Pharmacokinetics of imipramine are affected by age and sex in rats.

Chronic treatment with the antidepressant imipramine (IMI) leads to accumulation of imipramine's major metabolite desmethylimipramine (DMI) in the brain. Juvenile, young and middle-aged female rats, as well as juvenile and young male rats were treated chronically with imipramine (14 days) and analyzed 24 hours later for levels of IMI and DMI in the hypothalamus-preoptic area (HPA) and serum. Older animals of both sexes showed higher levels of DMI than juvenile animals, in both the HPA and serum. Females also had higher DMI levels than males at comparable ages. Analysis of IMI and DMI levels at intervals after a single imipramine injection suggested that the initial metabolism of imipramine is slower in older animals and in females (compared to males). The results indicate that age and gender alter the initial metabolism of imipramine, leading to enhanced accumulation of metabolites during chronic treatment in older animals and in female rats, compared to younger rats and males, respectively.

Aging↗

Preservation of steroid receptors in frozen brain and pituitary tissue: use of the cryoprotective agent, dimethylsulfoxide.

This paper examines the effects of freezing and thawing on steroid receptor concentrations in the brain and pituitary of the rat. Storage at -70 degrees C for 1-2 weeks had no detectable effect on levels of cytoplasmic estrogen receptors. However, freezing and thawing resulted in measurable losses of cytoplasmic androgen, progestin and glucocorticoid receptors. Cell nuclear receptors were measured by exchange assay after in vivo administration of non-radioactive steroids. Nuclear estrogen, androgen and progestin receptor concentrations were all reduced by freezing compared to the levels in fresh tissue. In all cases except that of cytoplasmic glucocorticoid receptors, these losses could be prevented by freezing the tissue in 10% aqueous dimethylsulfoxide.

Animals↗

Estrogen-induced progestin receptors in the brain and pituitary of the South African clawed frog, Xenopus laevis.

High-affinity progestin binding sites were found in the brain and pituitary of the female South African clawed frog, Xenopus laevis. Cytosol progestin receptors in the hypothalamus-preoptic area and pituitary were increased in number by estradiol treatment in ovariectomized frogs. The telencephalon also contained high-affinity binding sites, but the concentration was not affected by estrogen priming. Autoradiographic analysis of the distribution of the synthetic progestin 3H-R5020 revealed some lightly labeled cells in the anterior preoptic area and ventral infundibulum of ovariectomized animals. After estrogen priming, many heavily labeled cells were observed in the following areas: ventrolateral striatum and amygdala, anterior preoptic area, ventral infundibular nucleus, laminar nucleus of the torus semicircularis, and anterior pituitary. The areas in which dense accumulations of 3H-R5020 labeled cells were found after estrogen treatment are a subset of areas known to contain estrogen binding sites. The induction of progestin receptors by estradiol may be related to the requirement for both estrogen and progestin to elicit female sexual behavior in this species.

Animals↗

Inhibition of sexual receptivity by anesthesia during estrogen priming.

Anesthetics such as pentobarbital have been used to infer a role of neural activity in several neuroendocrine responses. The present experiments tested the hypothesis that neural activity during estrogen priming is necessary for the induction of sexual receptivity. Sexual behavior was induced in ovariectomized female rats by two pulses of unesterified estradiol 6 h apart, followed by progesterone at 19 h and testing at 24 h. Anesthetizing animals for approximately 1 h during each exposure to estradiol inhibited the induction of receptivity. Anesthesia immediately before each exposure to estradiol did not interfere with the induction of sexual receptivity. The induction of neural progestin receptors by estradiol was not prevented by anesthesia. Anesthesia had no effect on the uterine weight response to estradiol. These results suggest that neural activity during estrogen priming is required for the induction of sexual receptivity, and point to differences in the mechanism of action of estrogens in the brain and the uterus.

Anesthesia↗

A possible physiological basis for the dud-stud phenomenon.

Intact male rats were tested on two successive weekly tests with females to determine their level of sexual activity. Nuclear estrogen receptor content was measured in specific brain regions of individual sexually responsive and sexually nonresponsive males. Sexually nonresponsive male rats had significantly reduced nuclear estrogen receptor levels in the preoptic area compared to sexually responsive males. Sexually active males did not differ from inactive males in nuclear estrogen receptors in the medialbasal hypothalamus.

Animals↗

Adrenalectomy fails to alter radial maze performance of rats at retention intervals of 24 hours or less.

Evidence suggests that the behavioral actions of adrenalectomy and glucocorticoid replacement therapy result from changes in the binding of corticosterone to specific receptors in the hippocampus. Efficient foraging for bait on the radial maze has been demonstrated to require a functionally intact hippocampal system. The present experiment examined the effect of adrenalectomy on the ability of rats to locate unexplored arms in the radial maze after various retention intervals midway through completion of the maze. Rats were very proficient at locating the unexplored arms after retention intervals of 3 hours or less; significantly more trials were required to locate all of the previously unvisited arms at retention intervals of 8 and 24 hours. However, adrenalectomy failed to alter maze performance at any retention interval tested. It was concluded that the neural substrates involved in the performance of this spatial/working memory task are not dependent upon the neuromodulatory effects of physiological levels of adrenal corticosteroids. The results are discussed in terms of behavior/contingency conflicts and innate versus learned responses as factors which may be important for revealing behavioral actions of adrenalectomy or corticosteroid therapy.

Adrenal Cortex Hormones↗

Behavioral insensitivity to progesterone during lactation in female rats.

Lactating female rats failed to display sexual receptivity after receiving 50 micrograms of estradiol benzoate followed by 1 mg of progesterone. Lactating rats appear to be insensitive to progesterone, based on several experiments. In ovariectomized control rats receiving moderate estrogen priming (1 microgram EB for 3 days), progesterone greatly facilitated sexual receptivity; similarly estrogen-primed lactating females showed no responsiveness to progesterone injections, even at a high dose of progesterone (10 mg). Consistent with this reduced behavioral responsiveness to progesterone, lactating females had significantly reduced nuclear progestin receptor levels after an injection of 1 mg progesterone compared to ovariectomized controls. On the other hand, both ovariectomized controls and lactating rats responded with high levels of receptivity to 3 days of priming with 10 micrograms of estradiol benzoate (without progesterone). Lactating females treated for 3 days with a moderate dose (1 microgram) of estradiol benzoate showed slightly reduced receptivity compared to ovariectomized controls; this result could reflect a reduced sensitivity to estrogen but is more likely related to the somewhat lower serum levels of estradiol and consequently lower nuclear estrogen leading to a reduced sensitivity to progesterone cannot be eliminated (since animals respond to progesterone only after estrogen priming); however, the reported results favor the idea that lactating females are primarily refractory to progesterone and do not have a generalized insensitivity to estrogen.

Animals↗

Age alters the observed response of imipramine binding sites to chronic antidepressant treatment in female rats.

Age alters hypothalamic imipramine binding sites in female rats. Older females have increased levels of imipramine binding with decreased affinity. The response of hypothalamic imipramine binding sites to chronic antidepressant treatment varies depending on the age of the animals treated. In juvenile female rats imipramine binding sites decrease after antidepressant treatment, consistent with previous reports. However, in young females chronic imipramine treatment produces no change in levels of imipramine binding with a slight decrease in binding affinity. In middle-aged female rats, the same treatment causes an apparent increase in levels of imipramine binding sites along with a decrease in affinity. These decreases in the affinity of imipramine binding sites in older female rats, and the concomitant changes in the levels of imipramine binding are the result of imipramine metabolites remaining in the tissue after antidepressant treatment and interfering with the binding assay, despite extensive washing of the membrane preparation. Thus, the observed changes in the response of imipramine binding sites to chronic imipramine treatment with age are probably due to age-related alterations in the metabolism of imipramine in female rats.

Aging↗

Behavioral and cellular responses to pulses of low doses of estradiol-17 beta.

The effectiveness of single vs. separate pulses of low doses of free estradiol on the induction of sexual receptivity in ovariectomized female rats was examined. Two separate subcutaneous pulses of low doses of free estradiol at 0 and 6 hours induced high levels of progesterone facilitated receptivity at 24 hours. However, a single pulse of the same total dose of estradiol induced little or no receptivity at 24 hours (or at 18 hours). In fact, approximately 10 times as much estradiol was required in a single pulse to induce comparable receptivity. The smaller behavioral response to a single pulse was not likely due to a ceiling effect or an unutilized excess of the hormone after one injection. This suggestion is based on measurements of the redistribution of estrogen receptors from the cytoplasm to cell nuclei as an index of an initial cellular stimulus. Doses of estradiol used in the behavioral studies included several doses that were subsaturating with regard to hypothalamic estrogen receptors. The greatly enhanced behavioral response to two separated pulses of estradiol is consistent with the hypothesis that an initial action of estradiol may be to sensitize target tissues to further stimulation by the hormone.

Animals↗

Age alters dopaminergic responses to estradiol.

Young (3-5 months) and middle-aged (17-19 months) ovariectomized rats were treated with estradiol benzoate for three days and striatal dopaminergic function was assessed behaviorally (circling in response to apomorphine) and neurochemically (binding of [3H]spiroperidol by striatal membranes). The results suggest that striatal dopaminergic function may respond differently to estrogen in older animals compared to younger animals.

Aging↗

Diurnal rhythm of cytoplasmic estrogen receptors in the rat brain in the absence of circulating estrogens.

The concentration of cytoplasmic estrogen receptors in the brain of ovariectomized female rats varies during the light-dark cycle. There is no variation in the affinity of the receptors for estradiol, and the rhythm is not due to estrogens from nonovarian sources. Pentobarbital reverses the reduction of receptors that occurs in the dark, and melatonin injection in the light partially mimics the action of darkness in reducing receptor levels. The factors that cause this rhythm is brain estrogen receptors may be one means by which light affects reproductive function.

Adrenalectomy↗